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From a taxonomic point of view, Hymenoptera are subclassified into families: Apidae, including honeybees (Apis mellifera) and bumblebees (Bombus), and Vespidae, which, in turn, are divided into the subfamilies of Vespinae (wasps, including hornets, vespules, dolichovespules) and Polistinae (paper wasp). Hypersensitivity to Hymenoptera venom can be linked to immunological (IgE-mediated or non-IgE-mediated) and non-immunological mechanisms. Reactions are classified into local reactions, large local reactions, systemic reactions, toxic reactions, and unusual reactions. In general, children sensitize less frequently and have less severe reactions than adults, probably due to less exposure to repeated stings and fewer comorbidities. There are risk factors for systemic reactions that should be discussed with patients and their parents as appropriate. A correct diagnosis of Hymenoptera venom allergy relies on a careful clinical history and the appropriate use of skin and in vitro tests. The in vitro tests include serum specific IgE toward venom extracts and toward allergenic molecules. In complex diagnoses, CAP-inhibition and the Basophil Activation Test can also be used. In the presence of a systemic reaction, the basal serum tryptase measurement should be performed to rule out mastocytosis. In case of allergic reactions to Hymenoptera stings, in the acute phase, according to the current guidelines, the treatment of signs and symptoms mainly includes the use of adrenaline as first-line treatment in case of anaphylaxis and antihistamines and corticosteroids as subsequent lines of treatment. Given the impossibility of avoiding a new sting with certainty, the treatment of choice in subjects with hypersensitivity to Hymenoptera venom who have experienced systemic reactions is based on venom immunotherapy (VIT), with the venom of the responsible stinging insect identified after an adequate allergological work-up. VIT is performed in a suitable environment and has proved to be safe and effective with various administration protocols, both accelerated and conventional. The prevention of Hymenoptera venom anaphylaxis in patients who have already developed a previous episode is crucial and must be supported by environmental protection interventions and early therapy. Places where one is more likely to encounter insects and risky behaviors should be avoided. [ABSTRACT FROM AUTHOR]

The Nuclear factor erythroid 2–related factor (Nrf2)/ Heme oxygenase-1 (HO-1) pathway, known for its significant role in regulating innate antioxidant defense mechanisms, is increasingly being recognized for its potential in neuroprotection studies. Derived from bee venom, melittin's neuroprotective effects have raised interest. This study confirmed that melittin specificity upregulated the weakened Nrf2/HO-1 signaling in mice brain. Interestingly, we also revealed melittin's efficient tactic, as it was suggested to first restore redox balance and then gradually stabilized other regulations of the mouse hippocampus. Using a neuro-stress-induced scopolamine model, chromatography and mass spectrometry analysis revealed that melittin crossed the compromised blood–brain barrier and accumulated in the hippocampus, which provided the chance to interact directly to weakened neurons. A wide range of improvements of melittin action were observed from various tests from behavior Morris water maze, Y maze test to immune florescent staining, western blots. As we need to find out what is the focus of melittin action, we conducted a careful observation in mice which showed that: the first signs of changes, in the hippocampus, within 5 h after melittin administration were the restoration of the Nrf2/HO-1 system and suppression of oxidative stress. After this event, from 7 to 12.5 h after administration, a diversity of conditions was all ameliorated: inflammation, apoptosis, neurotrophic factors, cholinergic function, and tissue ATP level. This chain reaction underscores that melittin focus was on redox balance's role, which revived multiple neuronal functions. Evidence of enhancement in the mouse hippocampus led to further exploration with hippocampal cell line HT22 model. Immunofluorescence analysis showed melittin-induced Nrf2 translocation to the nucleus, which would initiating the translation of antioxidant genes like HO-1. Pathway inhibitors pinpointed melittin's direct influence on the Nrf2/HO-1 pathway. 3D docking models and pull-down assays suggested melittin's direct interaction with Keap1, the regulator of the Nrf2/HO-1 pathway. Overall, this study not only highlighted melittin specifically effect on Nrf2/HO-1, thus rebalancing cellular redox, and also showed that this is an effective multi-faceted therapeutic strategy against neurodegeneration. [ABSTRACT FROM AUTHOR]

Black widows, one of the few spiders that can sting humans with poison, are members of the spider genus Latrodectus and are well-known for the extraordinary potency of their neurotoxic venom. Latrodectism, a symptom marked by excruciating muscular pain, stomach pain, and diaphoresis after envenomation, is very typical. We described a black widow envenomation case that produced a significant reaction, including diaphoresis and excruciating pain throughout the left thigh that later spread to the lower leg, lower back, belly, and chest. Because of the patient's description of the spider that bit him and his typical clinical state, it was assumed that Latrodectus envenomation was the cause of his symptoms. The patient received 3 days of observation in the ED while receiving opioid analgesic pain management and muscle relaxant treatment with diazepam. The patient's pain and symptoms were satisfactorily managed, and he was sent home. This case report will help further research be done in the area where it was reported to see if there are cases with similar presentations misdiagnosed as other illnesses. Finally, immediate pain relief is the most critical goal for all patients. [ABSTRACT FROM AUTHOR]

Background: Tilapia Piscidin 4 (TP4) showed potential anti-tumor effects against various cancer cells. Lycosine-1 (LYC1), is another Antimicrobial Peptides (AMP) from spider venom with targeted penetration to cancer cells without any adverse effects on normal cells. The aim of this study was to produce a soluble recombinant fusion peptide in order to diminish the cytotoxicity of TP4 against normal cells. Methods: In order to express of TP4-LYC-1, TP4, and LYC1 in fusion to the inteins1/2 of pTWIN-1 vector, induction condition was optimized to earn soluble peptides. Autocleavage induction of inteins1/2 was performed based on IMPACT® manual and their effect on cell viability of HeLa and HUVEC cells was surveyed by MTT assay. Results: The best condition for accessing the most soluble peptide in fusion to the inteins was approximately similar for all three peptides (0.1 mM of IPTG, at 22°C). After the induction of self-cleavage of inteins, a band in 3, 3, and 6 kDa was observed on tricine- SDS-PAGE. The IC50 values of TP4-LYC1 and TP4 against HeLa cells were calculated as 0.83, and 2.75 µM, respectively. Conclusion: In the present study, a novel chimeric peptide, TP4-LYC1, was successfully produced. This fusion protein can act as a safe bio-molecule with potent cytotoxic effects against cancer cells, but the penetration ability and determination of cell death mechanism must be performed in order to have more precise view on the apoptosis induction of this recombinant peptide. [ABSTRACT FROM AUTHOR]

Background: Maintenance of immune system integrity is a vital requirement to protect human body against pathogens/cancers. Natural compounds have long been used due to their benefits for the immune system. One of which is bee venom that contains a peptide called melittin having antimicrobial and anticancer effects. Since a limited number of studies regarding the effects of melittin on the immune system have been carried out, we aimed to evaluate the effects of melittin on BALB/c mice immune system parameters. Methods: Female BALB /c mice were treated intraperitoneally (i.p) with 0.75 and 1.5 mg/kg doses of melittin for 14 days (5 doses per week). The negative control group received i.p normal saline whereas the positive controls received i.p 20 mg/kg cyclophosphamide (CYP). Immunological parameters such as hematological parameters, delayed-type hypersensitivity (DTH), hemagglutination titer (HA), spleen cellularity, splenocytes proliferation, as well as spleen and bone marrow histopathological assessment were evaluated. Results: Our findings showed that melittin has no gross pathological effect on the spleen and bone marrow. It was also demonstrated that melittin has no any significant effect on hematological parameters. Melittin did not cause any significant changes to proliferation response of splenocytes to PHA and LPS, spleen cellularity, DTH response, as well as the production of anti-SRBC antibodies. According to our results, melittin at 0.75 and 1.5 mg/kg doses could not induce significant changes on immune parameters and as a result, melittin was found to be safe for the mice immune system. [ABSTRACT FROM AUTHOR]

Introduction: Burn wounds caused by monopolar or bipolar cautery, which are common in surgical practice, can lead to serious complications in the post-operative period. We observed that psalmotoxin-1 (Pctx1) induces an inflammatory response during the burn-healing process and creates an effective wound-healing process. It also triggered the development of granulation tissue. Thanks to this venom, complications that may occur can be prevented in the early period. Methods: In this experimental study, 18 healthy, 300-350 g weighted, adult (aged>5 months) male Wistar rats were randomly assigned to 2 groups. Group 1 (n=9) was the control group. Group 2 (n=9) was burned and treated with PCTx1 0,1cc/kg IP. Post-recovery burn areas were evaluated by immunohistochemical staining. All samples were classified in terms of tissue repair response (TRR) values (inflammation, fibrosis, neovascularization, and epithelization) and other examination criteria of bacterial colonization and bleeding. Results: PCTx1 helped the wound healing process and when the inflammation, fibrosis, epithelization values of neovascularization, and other TRR values were examined, they were found to be significantly different compared to the control group 1 (p<0.05). In addition, the bacterial colonization and bleeding values of control group 1 were found to be significantly higher than group 2 (PcTx1) (p<0.05). According to histopathological examination, more granulation tissue and neovascularization were observed in the epidermis and wound area in Group 2 than in Group 1. In Group 2 (burn group treated with PcTx1), intense healing was observed characterized by the formation of well-organized granulation tissue in the epidermis and dermis. PcTx1 was also observed to be more effective by accelerating inflammation. Discussion and Conclusion: Using PcTx1 in the wound healing process of burns, completing the remodeling phase of wound healing. We observe that this venom has the potential to be considered among the treatment options for such injuries in the future. [ABSTRACT FROM AUTHOR]

Introduction: The scorpion of Androctonus crassicauda belongs to the Buthidae family, it has a strong and deadly venom for humans, and every year there are cases of death due to the sting of this scorpion. The purpose of this study is the biological evaluation of the venom of this scorpion, the production of monovalent antivenom against it, and the evaluation of the effectiveness of the produced antivenom. Methods: The A. crassicauda scorpions were collected from different cities of Khuzestan province and milked by electric shock. In this research, the amount of venom protein, lethal dose 50 (LD50), immune response of horses, purification of antibodies, effectiveness of antivenom (ED50), degree of neutralization of venom with antivenom and the effect of monovalan antivenom in neutralizing the activity of hyaluronidase enzyme were evaluated. This research has been approved by the Ethics Committee of the Razi Vaccine and Serum Research Institute with code IR.RVSRI.REC.1401.017. Results: The amount of protein and LD50 of the venom from studied scorpion were calculated to be 78 mg/ml and 11.27 µg per mouse, respectively. The results of measuring the antibody titer at different times of venom injection showed the increase in the immune response of horses against the venom. The value of ED50 was around 9 LD50 and 92.22 µg per mouse. According to the results, scorpion venom has hyaluronidase enzyme activity, and 10 µL of the produced pure antivenom was able to neutralize 100% of the venom's hyaluronidase activity. Conclusions: In this project, extracted venom and produced antivenom showed their effectiveness. The produced antivenom was able to neutralize the venom in mice and prevented the death of the envenomed mice [ABSTRACT FROM AUTHOR]

Simple Summary: The beneficial effects of natural substances that have been used in medicine for many years require both scientific confirmation and recognition of the mechanism of their action. In this paper, we present the current state of knowledge regarding the mechanisms of anticancer activity of bee venom in in vitro and animal model studies. So far, research shows strong anti-cancer potential of both crude bee venom and its main constituent, melittin, by inducing apoptosis and inhibiting the cell cycle without significantly affecting physiological cells. Increasingly frequent animal studies indicate the safety of venom doses that are effective in in vitro studies. This information can help plan future clinical trials. Honey bee venom in its composition contains many biologically active peptides and enzymes that are effective in the fight against diseases of various etiologies. The history of the use of bee venom for medicinal purposes dates back thousands of years. There are many reports in the literature on the pharmacological properties of bee venom and/or its main components, e.g., anti-arthritic, anti-inflammatory, anti-microbial or neuroprotective properties. In addition, both crude venom and melittin exhibit cytotoxic activity against a wide range of tumor cells, with significant anti-metastatic activity in pre-clinical studies. Due to the constantly increasing incidence of cancer, the development of new therapeutic strategies in oncology is a particular challenge for modern medicine. A review paper discusses the various properties of bee venom with an emphasis on its anticancer properties. For this purpose, the PubMed database was searched, and publications related to "bee", "venom", "cancer" from the last 10 years were selected. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma multiforme (GB) and neuroblastomas (NBs) are nervous system cancers that are difficult to diagnosis and treat. Chlorotoxin (CTX), is a peptide extracted from scorpion venom which easily binds with many cancer cells, especially in GB and NB. Through nanotechnological methods, CTX can be conjugated to nanoparticles (NPs), and used both as for both diagnostic and therapeutic (theranostics) applications. This review article discusses the potential use of CTX-NP formulations for GB and NB, provides the current understanding of the mechanisms by which CTX may cross the difficult blood-brain barrier to target tumour cells. The authors extensively discuss the current state of research involving similar formulations and suggest areas for further investigation, such as using CTX-NPs for hyperthermia-based treatments therapy. Furthermore, the article discusses future trends and perspectives for novel CTX-based NP formulations to revolutionize the diagnosis and treatment of these challenging brain tumours. Glioblastoma multiforme (GB) and high-risk neuroblastoma (NB) are known to have poor therapeutic outcomes. As for most cancers, chemotherapy and radiotherapy are the current mainstay treatments for GB and NB. However, the known limitations of systemic toxicity, drug resistance, poor targeted delivery, and inability to access the blood-brain barrier (BBB), make these treatments less satisfactory. Other treatment options have been investigated in many studies in the literature, especially nutraceutical and naturopathic products, most of which have also been reported to be poorly effective against these cancer types. This necessitates the development of treatment strategies with the potential to cross the BBB and specifically target cancer cells. Compounds that target the endopeptidase, matrix metalloproteinase 2 (MMP-2), have been reported to offer therapeutic insights for GB and NB since MMP-2 is known to be over-expressed in these cancers and plays significant roles in such physiological processes as angiogenesis, metastasis, and cellular invasion. Chlorotoxin (CTX) is a promising 36-amino acid peptide isolated from the venom of the deathstalker scorpion, Leiurus quinquestriatus, demonstrating high selectivity and binding affinity to a broad-spectrum of cancers, especially GB and NB through specific molecular targets, including MMP-2. The favorable characteristics of nanoparticles (NPs) such as their small sizes, large surface area for active targeting, BBB permeability, etc. make CTX-functionalized NPs (CTX-NPs) promising diagnostic and therapeutic applications for addressing the many challenges associated with these cancers. CTX-NPs may function by improving diffusion through the BBB, enabling increased localization of chemotherapeutic and genotherapeutic drugs to diseased cells specifically, enhancing imaging modalities such as magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), optical imaging techniques, image-guided surgery, as well as improving the sensitization of radio-resistant cells to radiotherapy treatment. This review discusses the characteristics of GB and NB cancers, related treatment challenges as well as the potential of CTX and its functionalized NP formulations as targeting systems for diagnostic, therapeutic, and theranostic purposes. It also provides insights into the potential mechanisms through which CTX crosses the BBB to bind cancer cells and provides suggestions for the development and application of novel CTX-based formulations for the diagnosis and treatment of GB and NB in the future. [ABSTRACT FROM AUTHOR]

Background: Envenomation caused by snakebites and scorpion stings is a neglected disease responsible for significant morbidity and mortality. In Qatar, little information is available on the epidemiological aspects of snakebites and scorpion stings. This study describes the demographic and epidemiological characteristics of patients treated for scorpion stings or snakebites at Qatar's Primary Health Care Corporation (PHCC). Methods: A retrospective data analysis was applied to investigate the number of scorpion stings and snakebites reported at the PHCC health centers between January 1, 2018, and December 31, 2022. The data were electronically extracted from the medical records of the registered population at PHCC. Results: 581 scorpion stings and 21 cases of snakebites were reported between January 1, 2018, and December 31, 2022. The highest number of scorpion stings reported in 2020 was 141 cases. The distribution of scorpion stings was higher among males than females, with rates of 86% and 14%, respectively, and the highest number of cases occurred in the age group of 19-39 years. Among the total cases, Bangladeshi and Qatari were the most affected, with a rate of 41% and 14%, respectively. The western region had the highest incidence of scorpion stings, at 7.47 per 10,000 persons. Conclusion: According to this research, the western region had the highest occurrence of scorpion stings cases, primarily among Bangladeshis and Qataris, particularly in the age group of 19-49 years. This study also found similar patterns in snakebite cases. Consequently, this study emphasizes the need for increased investment in antivenom and the training of healthcare professionals to address scorpion stings effectively. [ABSTRACT FROM AUTHOR]

Epithelial–mesenchymal transition (EMT) causes polarized and cohesive epithelial cells to become motile and join the extracellular matrix (ECM). Embryonic development, wound healing, and tissue repair need it. Interestingly, the same mechanism may cause cancer, organ fibrosis, scarring, and organ failure. WNT, Notch, Hedgehog, and RTK signaling impact EMT. This process also includes nontranscriptional changes due to growth hormones, cytokines, hypoxia, and ECM interaction. The reason for the development of oral submucous fibrosis (OSF) is believed to be multifaceted; nevertheless, there is substantial evidence supporting the notion that it arises from dysregulation of collagen. EMT is a prominent phenomenon in the development of OSF, whereby myofibroblasts and keratinocytes are the cells most affected. The role of EMTs is crucial in both physiological and pathological processes. The significance of EMT involvement in the pathogenesis of OSF and the preceding inflammatory response suggests a promising avenue for further investigation. Transforming growth factor‑1 (TGF‑1) plays a crucial role in the EMT of oral keratinocytes that initiates the pathogenesis of OSF. The objective of this review is to analyze the events of EMT in OSF, along with the processes and molecular routes that regulate alterations in gene expression within the oral cavity. The potential for cancerous transformation is linked to OSF, prompting an examination of the involvement of apamin in the advancement of EMT triggered by TGF‑1 in oral keratinocytes. [ABSTRACT FROM AUTHOR]

Snakebite envenoming (SBE) is a global health challenge, predominantly affecting economically disadvantaged regions. India contributes significantly to global snakebite mortality. Since 2013, the Indian Council of Medical Research (ICMR) has spearheaded efforts to combat SBE. A multi-sectoral engagement in the snakebite research projects and inputs from communities, traditional healers, and the health system have led to the creation of an Information Education and Communication (IEC) material suite, including management flowchart, information booklets, posters, and brochures, all available in local languages. These resources were broadly disseminated in high-burden regions in Maharashtra and Odisha, resulting in an approximately 10% increase in case reporting within a year. This holistic approach, engaging diverse stakeholders and addressing multiple facets of SBE, offers promise for alleviating the snakebite burden, not only in India but also in other low- and middle-income countries across South Asia, Africa, and South America, holding potential for broader positive global impact. [ABSTRACT FROM AUTHOR]

Background: Apitherapy is an emerging field in cancer research, particularly in developing communities. The potency of Melittin (MEL), a major constituent in bee venom is accounted for the cytotoxic capacity against cancer cells. It is postulated that the genotype of bees and the time of venom collection influences its specific activity against certain types of cancer. Method: Hereby, Jordanian crude bee venom (JCBV) was collected during different seasons of the year, specifically spring, summer and autumn and investigated for in vitro antitumour effects. Venom collected during springtime comprised the highest quantity of MEL in comparison to venom collected some other time. Springtime-collected JCBV extract and MEL were tested on an immortal myelogenous leukaemia cell line, namely K562 leukemic cells. Treated cells were examined for cell modality via flow cytometry analysis and cell death mediating gene expressions. Results: Springtime-collected JCBV extract and MEL showed an IC50 of 3.7 ± 0.37 μg/ml and 1.84 ± 0.75 μg/ml, respectively. In comparison to JCBV and positive control, MEL-treated cells exhibited late apoptotic death with a moderate cellular arrest at G0/G1 and an increase of cell number at G2/M phase. Expression of NF-κB/MAPK14 axis was inhibited in MEL and JCBV-treated cells, as well as expression of c-MYC and CDK4. Moreover, marked upregulation in ABL1, JUN and TNF was observed. In conclusion, springtime-collected JCBV showed the highest content of MEL while both JCBV and pure MEL showed apoptotic, necrotic, and cell cycle arrest efficiency against K562 leukemic cells. Conclusion: Integration of bee venom in chemotherapy needs more investigation and should be carefully translated into clinical use. During such translation, the correlation of bee genotype, collection time and concentration of MEL in CBV should be profiled. [ABSTRACT FROM AUTHOR]

Processed Buthus martensii Karsch (BmK) scorpion, also known as Quan-Xie, is a traditional Chinese medicine that is clinically used for the treatment of NAFLD due to its Tong-Luo-San-Jie effects. Our previous study showed that aqueous extract of processed BmK scorpion venom gland (pVg AE) inhibited macrophage inflammation by targeting Kv1.3 and identified the thermostable peptide BmKK2 as a potent Kv1.3 blocker. This study examined the therapeutic effects of processed BmK scorpions on NASH, specifically focusing on the involvement of their anti-inflammatory effects mediated by macrophage-expressed Kv1.3 in NASH. In the present study, the anti-NASH effects of pVg AE were evaluated in high-fat diet (HFD)-induced NASH mouse models. Additionally, the in vitro anti-inflammatory mechanisms of pVg AE and BmKK2 were assessed using a palmitic acid (PA)-induced mouse bone marrow-derived macrophages (BMDMs) inflammation model. Protein and cytokine expression related to the Kv1.3-NF-κB pathway was analyzed by real-time PCR, immunoblotting and ELISA. The effect of pVg AE and BmKK2 on potassium channels was detected by whole-cell voltage-clamp recordings on transfected HEK293T cells or mouse BMDMs. Calcium ion imaging was used to evaluate intracellular calcium signaling. Furthermore, the study utilized Kv1.3 siRNA and a BMDMs and hepatocytes co-culture model to investigate the specific role of Kv1.3 in mediating the anti-NASH effects of pVg AE and BmKK2. Lipid accumulation upregulated Kv1.3 expression in macrophages in vivo and in vitro. However, pVg AE significantly reduced Kv1.3 expression and Kv1.3-positive macrophage infiltration. Treatment with pVg AE improved obesity, insulin resistance (IR), hepatic steatosis (HS), inflammation, and fibrosis in HFD-fed mice. Mechanistically, pVg AE and BmKK2 inhibited macrophage inflammation by targeting Kv1.3, which reduced PA-induced intracellular Ca2+ levels, resulting in the inhibition of the NF-κB pathway and TNFα release. This study demonstrates that Kv1.3-mediated macrophage inflammation is involved in the pathogenesis and treatment of NASH. pVg AE effectively alleviates metabolic stress-induced NASH by inhibiting this inflammation. [Display omitted] • We demonstrated the role of Kv1.3 in the pathogenesis of NASH. • pVg AE mitigated metabolic stress-induced NASH by inhibiting Kv1.3-mediated inflammation in liver macrophages. • pVg AE and BmKK2 inhibited macrophage activation through Kv1.3-Calcium-NF-κB signaling. [ABSTRACT FROM AUTHOR]

Species of the Jatropha genus (Euphorbiaceae) are used indiscriminately in traditional medicine to treat accidents involving venomous animals. Jatropha mutabilis Baill., popularly known as "pinhão-de-seda," is found in the semi-arid region of Northeastern Brazil. It is widely used as a vermifuge, depurative, laxative, and antivenom. Obtaining the phytochemical profile of the latex of Jatropha mutabilis (JmLa) and evaluate its acute oral toxicity and inhibitory effects against the venom of the scorpion Tityus stigmurus (TstiV). The latex of J. mutabilis (JmLa) was obtained through in situ incisions in the stem and characterized using HPLC-ESI-QToF-MS. Acute oral toxicity was investigated in mice. The protein profile of T. stigmurus venom was obtained by electrophoresis. The ability of latex to interact with venom components (TstiV) was assessed using SDS-PAGE, UV–Vis scanning spectrum, and the neutralization of fibrinogenolytic and hyaluronidase activities. Additionally, the latex was evaluated in vivo for its ability to inhibit local edematogenic and nociceptive effects induced by the venom. The phytochemical profile of the latex revealed the presence of 75 compounds, including cyclic peptides, glycosides, phenolic compounds, alkaloids, coumarins, and terpenoids, among others. No signs of acute toxicity were observed at a dose of 2000 mg/kg (p.o.). The latex interacted with the protein profile of TstiV, inhibiting the venom's fibrinogenolytic and hyaluronidase activities by 100%. Additionally, the latex was able to mitigate local envenomation effects, reducing nociception by up to 56.5% and edema by up to 50% compared to the negative control group. The latex of Jatropha mutabilis exhibits a diverse phytochemical composition, containing numerous classes of metabolites. It does not present acute toxic effects in mice and has the ability to inhibit the enzymatic effects of Tityus stigmurus venom in vitro. Additionally, it reduces nociception and edema in vivo. These findings corroborate popular reports regarding the antivenom activity of this plant and indicate that the latex has potential for treating scorpionism. [Display omitted] • J. mutabilis is a medicinal plant of the semi-arid region of Northeastern Brazil. • The latex of J. mutabilis contains cyclic peptides and megastigmane glycosides. • The latex of J. mutabilis does not show acute toxicity in mice. • The latex of J. mutabilis inhibited venom hyaluronidase and fibrinogenolytic activities. • The latex of J. mutabilis reduced the edema and nociception induced by T. stigmurus venom. [ABSTRACT FROM AUTHOR]

An allergy to insect stings is one of the most frequent causes of anaphylactic reactions. Such reactions can be fatal, even on the first reaction, although it very rarely happens. The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) in refractory anaphylactic shock was previously described. We report a case of a 31-year-old female who presented with refractory anaphylactic shock after bee stings without the presence of cutaneous manifestations other than the rashes in her neck. The toxic component of bee venom and systemic allergic response plays a vital role in pathophysiology. She did not respond to conventional advanced life support, but following urgent VA ECMO, she survived neurologically intact. Despite an uncommon indication for anaphylaxis, ECMO support may be possible and effective in patients with refractory shock. [ABSTRACT FROM AUTHOR]

The article describes the role of nurses in determining symptoms of brown recluse spider bite with presentation of non-healing cellulitis. It cautions against complications of loxoscelism such as hemolytic anemia, acute kidney injury, rhabdomyolysis and disseminated intravascular coagulation, and describes its clinical presentation. It outlines nursing interventions for treatment of loxoscelism that may include intravenous fluids, antibiotics, plasmapheresis, wound care and possible dialysis.

Background: Poisoning due to scorpion stings and its consequences are among the health problems that remain current in the world. Scorpion stings are common in our region, especially in and around our city. Only a few of the more than 1500 scorpion species described in the world are very venomous and it is estimated that there are 15 species of scorpions in Turkey. In this study, the demographic data, epidemiological, clinical characteristics and results of the patients, which we followed up in our hospital' s intensive care unit (ICU) due to scorpion stings were evaluated. Materials and Methods: After obtaining the ethics committee approval, the archive data of the patients who were followed up and treated with the preliminary diagnosis of scorpion sting at Harran University Hospital between January 2013 and January 2023 were evaluated. The treatment approaches, epidemiological and clinical results in the general ICU, which were applied to adult patients with systemic symptoms and special conditions, were evaluated. Results: Of the 1493 patients included in our study who were treated in our hospital with the diagnosis of scorpion sting, 910 were patients aged >17 years. Of these, 74 were patients who were treated in the third level ICU. Of the patients treated in the adult ICU, 25.7% (n=19) were male and 74.3% (n=55) were female. The age of the patients ranged from 18 to 88 years. 43.6% (n=24) of the female patients were pregnant. The most common symptom was local pain (98.6%, n=73). It was observed that the lower (52.7%) and upper (44.6%) extremities were mostly affected. Of the patients, 70.3% (n=52) received tetanus antiserum for prophylactic purposes and 56.8% (n=42) received anti-venom treatment. Intravenous paracetamol was administered to pregnant patients as a pain reliever. Pregnant patients underwent obstetric USG at admission and before discharge, and they were discharged without any complications. It was observed that all of the patients were discharged with cure. Conclusions: Close follow-up and treatment in the ICU of patients with systemic symptoms due to scorpion stings and special conditions such as pregnancy may contribute to reducing mortality rates. Scorpion stings are frequently encountered in rural areas, especially in female patients and pregnant women. We think that this may be due to the fact that mostly women aged 15-49 work in agricultural areas in our region. We think that these results should be supported by more comprehensive public health studies. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for glioma. Melittin (MT) is the main component of bee venom, which was found to have therapeutic effects on a variety of tumors. In this study, we explored the relationship between key genes regulated by MT and the prognosis of glioma. In cultured glioma U87 and U251 cells, MT inhibited cell proliferation and induces cell apoptosis in a time- and concentration-dependent manner. RNA-seq revealed that MT upregulated 11 genes and downregulated 37 genes. These genes are mainly enriched in cell membrane signaling pathways, such as surface membrane, membrane-enclosed organelles, integral component of membrane, PPAR signaling pathway, and voltage-gated potassium channel. PPI network analysis and literature analysis of 48 genes were performed, and 8 key genes were identified, and these key genes were closely associated with clinical prognosis. Overexpression of PCDH18, PPL, DEPP1, VASN, KCNE4, MYBPH, and C5AR2 genes or low expression of MARCH4 gene in glioma patients was associated with poor survival. qPCR confirmed that MT can regulate the expression of these genes in glioma U87 cells. This study indicated that MT significantly inhibited the growth and regulated the expression of PCDH18, C5AR2, VASN, DEPP1, MYBPH, KCNE4, PPL, and MARCH4 genes in glioma U87 cells in vitro. These genes are closely related to the prognosis of patients with glioma and can be used as independent prognostic factors in patients with glioma. MT is a potential drug for the treatment of glioma. [ABSTRACT FROM AUTHOR]

In oriental medicine, bee venom has long been used as a therapeutic agent against inflammatory diseases. Several studies have reported that isolated and purified bee venom components are effective in treating dementia, arthritis, inflammation, bacterial infections, and cancer. In previous studies, we reported that bee venom inhibits cell growth and induces apoptotic cell death in lung cancer cells. In the present study, we assessed whether bee venom affects autophagy and thereby induces apoptosis. Bee venom treatment increased the levels of autophagy-related proteins (Atg5, Beclin-1, and LC3-II) and the accumulation of LC3 puncta. We found that bee venom could induce autophagy by inhibiting the mTOR signaling pathway. In addition, we found that hydroxychloroquine (HCQ)- or si-ATG5-induced autophagy inhibition further demoted bee venom-induced apoptosis. Bee venom-induced autophagy promotes apoptosis in lung cancer cells and may become a new approach to cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Venomous arthropods are arthropod species that use toxins for defense and offense. The objective of this study was to assess the biodiversity and abundance of venomous arthropods on the premises of Nnamdi Azikiwe University (NAU), Awka, Nigeria. Materials and Methods: Pitfall traps, sticky, and bait traps, beating and knockdown, and active search and handpicking with forceps were the methods used to collect various arthropods on the university campus. The data collected during this study were analyzed using the statistical package for social sciences version 23.0. Results: A total of 1,070 venomous arthropods were collected from the study areas, and they belong to four classes, six orders, fourteen families, and twenty-two species of the phylum Arthropoda. Conclusion: This study demonstrates that venomous arthropods are widespread on the NAU, Awka campus. Regular fumigation of the university premises is important in preventing human injuries, and infectious diseases carried by some arthropods.

Distinct animal lineages have convergently recruited venoms as weaponry for prey capture, anti-predator defence, conspecific competition, or a combination thereof. Most studies, however, have been primarily confined to a narrow taxonomic breadth. The venoms of cone snails, snakes, spiders and scorpions remain particularly well-investigated. Much less explored are the venoms of wasps (Order: Hymenoptera) that are infamous for causing excruciating and throbbing pain, justifying their apex position on Schmidt’s pain index, including some that are rated four on four. For example, the lesser banded wasp (V. affinis) is clinically important yet has only been the subject of a few studies, despite being commonly found across tropical and subtropical Asia. Stings from these wasps, especially from multiple individuals of a nest, often lead to clinically severe manifestations, including mastocytosis, myasthenia gravis, optic neuropathy, and life-threatening pathologies such as myocardial infarction and organ failure. However, their venom composition and activity remain unexplored in the Indian subcontinent. Here, we report the proteomic composition, transcriptomic profile, and biochemical and pharmacological activities of V. affinis venom from southern India. Our findings suggest that wasp venoms are rich in diverse toxins that facilitate antipredator defence. Biochemical and pharmacological assessments reveal that these toxins can exhibit significantly higher activities than their homologues in medically important snakes. Their ability to exert potent effects on diverse molecular targets makes them a treasure trove for discovering life-saving therapeutics. Fascinatingly, wasp venoms, being evolutionarily ancient, exhibit a greater degree of compositional and sequence conservation across very distant populations/species, which contrasts with the patterns of venom evolution observed in evolutionarily younger lineages, such as advanced snakes and cone snails.

Background: Allergy to Apis dorsata (Giant Asian Honeybee) venom is the commonest insect allergy in Sri Lanka and South East Asia. However, laboratory diagnosis is difficult as the pure venom and diagnostic reagents are not commercially available. Objective: This study assessed the use of four recombinant allergens of A. mellifera venom and the passive basophil activation test in the diagnosis of A. dorsata venom anaphylaxis. Methods: Serum IgE levels to four recombinant allergens of A. mellifera, rApi m 1, 2, 5 and 10 were assessed and compared with serum IgE to the crude venom of A. mellifera or V. vulgaris by Phadia ImmunoCAP, in patients who developed anaphylaxis to A. dorsata stings. Basophil activation in response to venom of A. dorsata or V. affinis was assessed using a passive basophil activation test. Association of the severity of the reaction with basophil activation was compared. Results: rApi m 1 and 10 combinedly had significant correlation (r = 0.722; p < 0.001) with the crude venom of A. mellifera (Western honeybee) and a higher positivity rate of 90% (27/30). Whereas, IgE reactivity to rApi m 2 or 5 had significant correlation (p = 0.02 and p = 0.005 respectively) with V. vulgaris crude venom. All 30 (100%) were positive to A. dorsata venom in passive BAT; 70% (21/30) had over 80% activation, 96.7% (29/30) had over 60% activation and 100% had over 50% activation. Percentage activation of basophils in patients who had mild or moderate reactions (n = 20) was significantly low (p = 0.02) from that of patients who had severe reactions (n = 10). Conclusions: rApi m 1 and 10 when combined was sensitive for the diagnosis of A. dorsata allergy. This combination had the lowest cross-reactivity rate with Vespula vulgaris. The passive BAT is highly sensitive in A. dorsata allergy. The basophil reactivity was significantly higher in severe anaphylaxis compared to mild/moderate anaphylaxis. This finding should be further explored in further studies. [ABSTRACT FROM AUTHOR]

Venoms from venomous arthropods, including bees, typically induce an immediate local inflammatory response; however, how venoms acutely elicit inflammatory response and which components induce an inflammatory response remain unknown. Moreover, the presence of superoxide dismutase (SOD3) in venom and its functional link to the acute inflammatory response has not been determined to date. Here, we confirmed that SOD3 in bee venom (bvSOD3) acts as an inducer of H2O2 production to promote acute inflammatory responses. In mouse models, exogenous bvSOD3 rapidly induced H2O2 overproduction through superoxides that are endogenously produced by melittin and phospholipase A2, which then upregulated caspase-1 activation and proinflammatory molecule secretion and promoted an acute inflammatory response. We also showed that the relatively severe noxious effect of bvSOD3 elevated a type 2 immune response and bvSOD3 immunization protected against venom-induced inflammation. Our findings provide a novel view of the mechanism underlying bee venom-induced acute inflammation and offer a new approach to therapeutic treatments for bee envenoming and bee venom preparations for venom therapy/immunotherapy. [ABSTRACT FROM AUTHOR]

The Mesobuthus martensii scorpions, called as "Quanxie", are known Chinese medicinal material base on the "Combat poison with poison" strategy for more than one thousand years, and still widely used to treat various diseases according to the Pharmacopoeia of the People's Republic of China nowadays. The study aims to investigate the similarity of scorpion neurotoxins at the protein level between the juvenile and adult Mesobuthus martensii scorpions as Chinese medicine materials. The second-, third- and fourth-instar, and adult Mesobuthus martensii scorpions were collected for the characterization of neurotoxin expression through multiple strategic proteomics, including undigested scorpion venom, endopeptidase-digested, and undigested scorpion telson extract for the sample analysis. Based on the known 107 scorpion neurotoxins from the genomic and transcriptomic analysis of adult Mesobuthus martensii scorpions, the multiple strategic proteomics first revealed that neurotoxins exhibited more stability in telson extract than secreted venom. In the reported transcripts of scorpion neurotoxins, approximately 53%, 56%, 66% and 78% of neurotoxins were detected through undigested scorpion venom, the endopeptidase Arg-C-, Lys-C-digested telson extract, and undigested telson extract strategies, respectively. Nearly 79% of scorpion neurotoxins detected in third-instar Mesobuthus martensii scorpions represent the largest number of scorpion neurotoxins from proteomic analysis to date. Moreover, a total of 84% of scorpion neurotoxins were successfully identified at the protein level, and similar neurotoxin expression profiles in second-, third- and fourth-instar, and adult Mesobuthus martensii scorpions were first revealed by the multiple strategic proteomics. These findings for the first time demonstrate the similar neurotoxin expression profiles between the juvenile and adult Mesobuthus martensii scorpions as Chinese medicinal material, which would serve as a paradigm for further toxin analysis from different venomous animals. [Display omitted] • Multiple strategic proteomics were utilized for neurotoxin characterization between juvenile and adult scorpions. • Neurotoxins of Mesobuthus martensii scorpion telson extract exhibited remarkable stability in multiple strategic proteomics. • 84% Mesobuthus martensii scorpion neurotoxins became the largest neurotoxin number from proteomic analysis. • Similar neurotoxin expression profiles existed in yound and adult Mesobuthus martensii scorpions. [ABSTRACT FROM AUTHOR]

Background: Anaphylaxis occurs in up to 3.5% of hymenoptera stings and can be a life-threatening emergency. Venom immunotherapy (VIT) provides excellent protection from further episodes of anaphylaxis and is well tolerated. In this study the frequency of anaphylactic reactions in pediatric patients undergoing rush bee venom immunotherapy was assessed as well as possible risk factors and modified up-dosing schemes are reported. Methods: 19 consecutive pediatric patients, who had previously experienced an anaphylactic reaction following a bee sting and showed IgE-mediated sensitization to bee venom, underwent inpatient rush immunotherapy with bee venom extract. We retrospectively compared serological findings (total IgE, serum tryptase level, sensitization to Api m1, Api m3 and Api m10 bee venom allergens) and possible risk factors between patients who experienced an anaphylactic reaction during immunotherapy and patients who did not. Results: Three of the included 19 patients (15.8%) developed anaphylactic reactions to rush bee venom immunotherapy, all of them between administration of 40 and 80 µg of bee venom extract. However, all three patients reached the standard maintenance dose of 100 µg of bee venom following a modified VIT schedule without any further complications. Total serum IgE levels as well as Api m3 sensitization levels were significantly higher in patients showing an adverse reaction to bee VIT compared to those who did not experience any complications. There were no statistically significant differences concerning age, pre-existing conditions, type and severity of the initial reaction and Api m1, Api m10 and serum tryptase levels between the two subgroups. Conclusion: Even if anaphylactic reactions occur during the build-up phase of VIT for bee venom in children and adolescents, venom immunotherapy can and should be continued in most cases. [ABSTRACT FROM AUTHOR]

Objective. Interstitial lung disease (ILD) is an important complication of systemic sclerosis (SSc). The aim of this study was to investigate the effect and possible mechanism of polypeptide extract of scorpion venom (PESV) on SSc-ILD. Methods. C57/BL6 mice were injected with bleomycin to establish a SSc-ILD model. Different concentrations of PESV solution were administered to SSc-ILD mice, and dexamethasone was used as a positive control. H&E staining and Masson staining were used to observe the pathological changes. The TGF-β1 expression level was detected by immunohistochemistry. The expression of epithelial-mesenchymal transition (EMT)-related proteins was detected by Western blot, and the expression of TGF-β1/Smad pathway-related proteins was also detected. The content of inflammatory cytokines in serum and BALF was determined by ELISA. Results. Pathological analysis showed that PESV could alleviate SSc-ILD-induced pulmonary inflammation and fibrosis. Compared with the model group, the content of inflammatory cytokines IL-6 and TNF-α significantly decreased after PESV treatment. PESV could increase the expression of epithelial marker (E-cadherin) and reduce the expression of interstitial markers (collagen I, vimentin, N-cadherin, and a-SMA). In addition, PESV could reduce the expression level of TGF-β1/Smad pathway-related protein. Conclusion. PESV can attenuate SSc-ILD by regulating EMT, and the effect was linked to the TGF-β1/Smad signaling pathway, which indicated that PESV may serve as a candidate drug for SSc-ILD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the general characteristics and warning signs for the more severe (grade 3) clinical course in severe scorpion envenomations in the pediatric intensive care unit (PICU). Methods: This retrospective, cross-sectional study was conducted in 12 beds tertiary care PICU in Antalya Training and Research Hospital. Patients admitted to the PICU between 2017-2021 due to severe scorpion envenomation were admitted to the study. Results: It was found that there were 2,208 admissions to the intensive care unit during the study period (4 years), and 73 (3.3%) of these cases (35 female and 38 male) were followed up for severe scorpion envenomation. The median age was 52 (26-89) months. Yellow scorpions were described by parents or eyewitnesses in 65 patients (89%) and black scorpions in 8 (11%). Peripheral sympathetic activity (cold extremities, diaphoresis) signs (n=55, 75.3%), hypertension (n=35, 47.9%), and tachycardia (n=21, 28%) were the most common findings. The most common echocardiographic findings were mild-to-moderate mitral regurgitation and systolic dysfunction in 31 (42.5%) and 19 (25.9%) cases, respectively. Sixty-two (89%) patients had grade 2 envenomations findings and 12 (11%) had grade 3. High pro-BNP, hyperglycemia, and hyperamylasemia were observed more frequently in grade 3 than in grade 2 patients on admission. All patients received anti-venom therapy and 7 (9.5%) of them required a second dose of anti-venom therapy due to the unregressed clinical course. Twenty-seven patients (37%) required inotropics, s and the most commonly used inotropics were milrinone in 17 (23.3%) patients and dobutamine in 12 (16.4%) patients. The median PICU length of stay was 4 (3-5) days and the median hospital stay was 5 (4-6) days. All patients survived to discharge. Conclusion: Hyperamilasemia, hyperglycemia, and elevated pro-BNP levels on admission may be warning signs of more severe (grade 3) patients. Mild-to-moderate mitral regurgitation may be more commonly observed echocardiography findings than systolic dysfunction in severe cases (grade 2 and 3). [ABSTRACT FROM AUTHOR]

Abstract: Gain-of-function and loss-of-function mutations in Nav1.7 cause chronic pain and pain insensitivity, respectively. The preferential expression of Nav1.7 in the peripheral nervous system and its role in human pain signaling make Nav1.7 a promising target for next-generation pain therapeutics. However, pharmacological agents have not fully recapitulated these pain phenotypes, and because of the lack of subtype-selective molecular modulators, the role of Nav1.7 in the perception of pain remains poorly understood. Scorpion venom is an excellent source of bioactive peptides that modulate various ion channels, including voltage-gated sodium (Nav) channels. Here, we demonstrate that Buthus martensii Karsch scorpion venom (BV) elicits pain responses in mice through direct enhancement of Nav1.7 activity and have identified Makatoxin-3, an α-like toxin, as a critical component for BV-mediated effects on Nav1.7. Blocking other Nav subtypes did not eliminate BV-evoked pain responses, supporting the pivotal role of Nav1.7 in BV-induced pain. Makatoxin-3 acts on the S3-S4 loop of voltage sensor domain IV (VSD4) of Nav1.7, which causes a hyperpolarizing shift in the steady-state fast inactivation and impairs inactivation kinetics. We also determined the key residues and structure-function relationships for the toxin-channel interactions, which are distinct from those of other well-studied α toxins. This study not only reveals a new mechanism underlying BV-evoked pain but also enriches our knowledge of key structural elements of scorpion toxins that are pivotal for toxin-Nav1.7 interactions, which facilitates the design of novel Nav1.7 selective modulators. [ABSTRACT FROM AUTHOR]

Abstract Accidents with venomous animals are a public health issue worldwide. Among the species involved in these accidents are scorpions, spiders, bees, wasps, and other members of the phylum Arthropoda. The knowledge of the function of proteins present in these venoms is important to guide diagnosis, therapeutics, besides being a source of a large variety of biotechnological active molecules. Although our understanding about the characteristics and function of arthropod venoms has been evolving in the last decades, a major aspect crucial for the function of these proteins remains poorly studied, the posttranslational modifications (PTMs). Comprehension of such modifications can contribute to better understanding the basis of envenomation, leading to improvements in the specificities of potential therapeutic toxins. Therefore, in this review, we bring to light protein/toxin PTMs in arthropod venoms by accessing the information present in the UniProtKB/Swiss-Prot database, including experimental and putative inferences. Then, we concentrate our discussion on the current knowledge on protein phosphorylation and glycosylation, highlighting the potential functionality of these modifications in arthropod venom. We also briefly describe general approaches to study “PTM-functional-venomics”, herein referred to the integration of PTM-venomics with a functional investigation of PTM impact on venom biology. Furthermore, we discuss the bottlenecks in toxinology studies covering PTM investigation. In conclusion, through the mining of PTMs in arthropod venoms, we observed a large gap in this field that limits our understanding on the biology of these venoms, affecting the diagnosis and therapeutics development. Hence, we encourage community efforts to draw attention to a better understanding of PTM in arthropod venom toxins.

Scorpion envenomation is a serious public health issue. Androctonus mauretanicus (Am) and Buthus occitanus (Bo) are the most dangerous scorpions in Morocco. Despite their medical relevance, no study has yet related their kinetics of symptom apparition and the consequent tissue disorders at the same interval post-injection. This work achieved the first comparative pathophysiological and toxic-symptoms study between the Am and Bo venoms from a biochemical, toxicological and physiopathological standpoint. The activity of venoms and their subletal dose were determined by administration of increasing concentrations of the venoms. 30, 60 and 120 min following the experimental envenomation in mice, the profile of clinical symptoms was underlined and the main organs: brain, heart, lungs, liver and kidneys were removed for histological examination. The Am venom is a rich source of proteins and three-times more toxic than the Bo. The most observed clinical symptoms are neurological and cardiopulmonary. The Am venom caused histopathological alterations at 30, 60, and 120 min which were more important than the Bo. This study highlighted that both venoms exhibited a strong toxicity with variable intensities. Moreover, we showed the presence of correlation between the level of histopathological disorders observed and the intensity of signs appeared at the same time following venom inoculation. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function.Methods: We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell-derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and postconditioning therapeutic agents.Results: Analysis of human complex trait genetics indicates that variants in the ASIC1 genetic locus are significantly associated with cardiac and cerebrovascular ischemic injuries. Using human induced pluripotent stem cell-derived cardiomyocytes in vitro and murine ex vivo heart models, we demonstrate that genetic ablation of ASIC1a improves cardiomyocyte viability after acute IRI. Therapeutic blockade of ASIC1a using specific and potent pharmacologic inhibitors recapitulates this cardioprotective effect. We used an in vivo model of myocardial infarction and 2 models of ex vivo donor heart procurement and storage as clinical models to show that ASIC1a inhibition improves post-IRI cardiac viability. Use of ASIC1a inhibitors as preconditioning or postconditioning agents provided equivalent cardioprotection to benchmark drugs, including the sodium-hydrogen exchange inhibitor zoniporide. At the cellular and whole organ level, we show that acute exposure to ASIC1a inhibitors has no effect on cardiac ion channels regulating baseline electromechanical coupling and physiologic performance.Conclusions: Our data provide compelling evidence for a novel pharmacologic strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI. [ABSTRACT FROM AUTHOR]

The scorpions, named Mesobuthus martensii, commonly called Quanxie (全蝎) in Chinese, have been widely used as one of the animal medicines for more than 1,000 years because of the strong toxicity of their venoms. Meanwhile, scorpions are sexually dimorphic in appearance, and many exhibit traits associated with sex-biased gene expression, including maternal care, mating competition, female mating choices, ecology, and even venom composition and lethality. This study aims to explore the differences in composition of the venom of scorpions of different sex using the method of transcriptomics. Whole de novo transcriptomes were performed on the samples of M. martensii captured from Gansu Province to identify their sex-biased gene expression. The conserved CO-1 sequences of the captured samples matched that of M. martensii. A total of 8,444 (35.15%), 7,636 (31.78%), 8,510 (35.42%), 7,840 (32.63%), 9,980 (41.54%), and 11,829 (49.23%) unigenes were annotated with GO, KEGG, Pfam, Swissprot, eggNOG, and NR databases. Moreover, a total of 43 metalloproteases, 40 potassium channel toxins, 24 phospholipases, 12 defensins, 10 peroxiredoxins, 9 cysteine proteinase inhibitors, 7 serine protease inhibitors, 6 sodium channel toxins, 2 NDBPs, 1 calcium channel toxin, 1 waprin-like peptide, 1 antibacterial peptide, 1 antimicrobial peptide, and 1 anticoagulant peptide were screened out. With the fold change of 2 and 0.5, p value < 0.01, and q value < 0.05 as thresholds, a total of 41 out of 157 (26.11%) toxin-related unigenes had significant differential expression, and this ratio was much higher than the ratio of differentially expressed unigenes out of all annotated ones (8.84%). Of these differentially expressed toxins, 28 were upregulated and occupied the majority, up to 68.30%. The female scorpions showed more upregulated unigenes that annotated with toxins and had the potential to be used as more effective therapeutic drugs. In addition, this method of omics can be further used as a useful way to identify the difference between female and male toxic animals. [ABSTRACT FROM AUTHOR]

Hymenoptera species include stinging insects such as wasps, hornets, bees, and fire ants. Allergic reaction to the venom of these insects is a common presenting complaint for patients in primary care and emergency medicine during warmer months. Patients' clinical presentations may vary, and clinicians must identify the type of reaction to determine treatment and follow-up plans. Treatment of patients allergic to Hymenoptera venom should be individualized based on risk factors, reaction type, and associated comorbidities. This article reviews common features of clinical presentation, diagnosis, and the current mainstays in management of Hymenoptera venom allergy. [ABSTRACT FROM AUTHOR]

Venoms from venomous arthropods, including bees, typically induce an immediate local inflammatory response; however, how venoms acutely elicit inflammatory response and which components induce an inflammatory response remain unknown. Moreover, the presence of superoxide dismutase (SOD3) in venom and its functional link to the acute inflammatory response has not been determined to date. Here, we confirmed that SOD3 in bee venom (bvSOD3) acts as an inducer of H2O2 production to promote acute inflammatory responses. In mouse models, exogenous bvSOD3 rapidly induced H2O2 overproduction through superoxides that are endogenously produced by melittin and phospholipase A2, which then upregulated caspase-1 activation and proinflammatory molecule secretion and promoted an acute inflammatory response. We also showed that the relatively severe noxious effect of bvSOD3 elevated a type 2 immune response and bvSOD3 immunization protected against venom-induced inflammation. Our findings provide a novel view of the mechanism underlying bee venom-induced acute inflammation and offer a new approach to therapeutic treatments for bee envenoming and bee venom preparations for venom therapy/immunotherapy.

Scorpion sting is a common public health problem worldwide and recent developments in research on the composition of scorpion poison and its therapeutic potential are promising. Some drugs based on these molecules are already in general practice use. The abuse of scorpion envenom is known in the history and in some recent publications from Asia and Africa. Some reports of medieval doctors also described the therapeutic use of this poison for analgesic, litholytic, anti-inflammatory and antimicrobial effect. Avicenna (or Ibn Sina, 980-1037) and his medieval colleagues were practitioners, toxicologists and researchers. They precisely described the uses and the danger of addiction of this poison. In this paper we review the literature. A PubMed search was done while using keywords: sting, stones, urolithiasis, medieval, chelation, scorpion, toxin. The findings showed that mastering urinalysis in medieval medicine was highly developed. The technique was accompanied by toxicological skills of the master. Using the scorpion envenom components in addition to its analgesic, antimicrobial effects, has by its chelating capabilities do dissolve and dislodge stones. This corresponds with recent research findings explaining the chelating effects of many of the peptides constituting the scorpion poison. [ABSTRACT FROM AUTHOR]

Background and Purpose: Protoxin II (ProTx II) is a high affinity gating modifier that is thought to selectively block the Nav 1.7 voltage-dependent Na+ channel, a major therapeutic target for the control of pain. We aimed at producing ProTx II analogues entitled with novel functionalities for cell distribution studies and biochemical characterization of its Nav channel targets.Experimental Approach: We took advantage of the high affinity properties of the peptide, combined to its slow off rate, to design a number of new tagged analogues useful for imaging and biochemistry purposes. We used high-throughput automated patch-clamp to identify the analogues best matching the native properties of ProTx II and validated them on various Nav -expressing cells in pull-down and cell distribution studies.Key Results: Two of the produced ProTx II analogues, Biot-ProTx II and ATTO488-ProTx II, best emulate the pharmacological properties of unlabelled ProTx II, whereas other analogues remain high affinity blockers of Nav 1.7. The biotinylated version of ProTx II efficiently works for the pull-down of several Nav isoforms tested in a concentration-dependent manner, whereas the fluorescent ATTO488-ProTx II specifically labels the Nav 1.7 channel over other Nav isoforms tested in various experimental conditions.Conclusions and Implications: The properties of these ProTx II analogues as tools for Nav channel purification and cell distribution studies pave the way for a better understanding of ProTx II channel receptors in pain and their pathophysiological implications in sensory neuronal processing. The new fluorescent ProTx II should also be useful in the design of new drug screening strategies. [ABSTRACT FROM AUTHOR]

Arthropods comprise the largest group of living animals, including thousands of species that inhabit marine and terrestrial niches in the biosphere [...]

The venom peptides disclosed correspond to two classes: bradykinin-related peptides (e.g., - and -campsomerin) and linear -helical peptides (e.g., annulatin). In a paper by Lopes and coworkers [[23]], they characterized a sphingomyelinase D (SMase D) from the venom of the spider I Sicarius tropicus. i They showed that the intrinsic features of this venom enzyme differ mechanistically from its counterpart in the venom of the spider I Loxosceles laeta i . Keywords: arthropod venom; venomics; venom peptides; structure-activity relationship; venom-derived peptide leads; venom-to-drug application EN arthropod venom venomics venom peptides structure-activity relationship venom-derived peptide leads venom-to-drug application N.PAG N.PAG 3 05/04/22 20220401 NES 220401 Arthropods comprise the largest group of living animals, including thousands of species that inhabit marine and terrestrial niches in the biosphere. Venom peptides, venom-derived peptide leads, venom-to-drug application, arthropod venom, venomics, structure-activity relationship. [Extracted from the article]

Background The objectives of this study were to assess the knowledge, attitudes and control practices among the staff and students of Nnamdi Azikiwe University (NAU), Awka, Anambra State, Nigeria, regarding venomous arthropods. Methods The knowledge, attitudes and control practices regarding venomous arthropods were assessed in 350 participants. Results The respondents were aware of the presence of venomous arthropods at NAU and they had seen them on campus, with spiders (40.44%) being the most common and electric ants (1.39%) being the least common. The control practices applied to limit the activities of these arthropods included keeping the environment clean (40.80%), the use of insecticides (37.33%), the use of repellents (8.68%), spraying houses with kerosene (7.81%), spraying of fuel on the arthropods (3.47%), screening of houses (1.39%) and the use of bed nets (0.52%). Conclusions An assessment and determination of knowledge, attitudes and control practices regarding venomous arthropods among the staff and students of NAU is necessary in order to improve the preventive measures to reduce injuries caused by venomous arthropod encounters, which are some of the most underestimated health hazards in tropical regions, including southeastern Nigeria, affecting primarily rural communities. According to the findings of our study, students and staff at NAU are rarely involved in life-threatening incidents as a result of their encounters with venomous arthropods and most apply several globally accepted standard practices for the control of venomous arthropods. [ABSTRACT FROM AUTHOR]

Scorpion Buthus martensii Karsch -analgesic-antitumor peptide (BmK AGAP) has been used to treat diseases like tetanus, tuberculosis, apoplexy, epilepsy, spasm, migraine headaches, rheumatic pain, and cancer in China. AGAP is a distinctive long-chain scorpion toxin with a molecular mass of 7142 Da and composed of 66 amino acids cross-linked by four disulfide bridges. Voltage-gated sodium channels (VGSCs) are present in excitable membranes and partakes in essential roles in action potentials generation as compared to the significant function of voltage-gated calcium channels (VGCCs). A total of nine genes (Nav1.1–Nav1.9) have been recognized to encode practical sodium channel isoforms. Nav1.3, Nav1.7, Nav1.8, and Nav1.9 have been recognized as potential targets for analgesics. Nav1.8 and Nav1.9 are associated with nociception initiated by inflammation signals in the neuronal pain pathway, while Nav1.8 is fundamental for neuropathic pain at low temperatures. AGAP has a sturdy inhibitory influence on both viscera and soma pain. AGAP potentiates the effects of MAPK inhibitors on neuropathic as well as inflammation-associated pain. AGAP downregulates the secretion of phosphorylated p38, phosphorylated JNK, and phosphorylated ERK 1/2 in vitro. AGAP has an analgesic activity which may be an effective therapeutic agent for pain management because of its downregulation of PTX3 via NF-κB and Wnt/beta-catenin signaling pathway. In cancers like colon cancer, breast cancer, lymphoma, and glioma, rAGAP was capable of blocking the proliferation. Thus, AGAP is a promising therapy for these tumors. Nevertheless, research is needed with other tumors. [ABSTRACT FROM AUTHOR]

Background: Members of the cysteine-rich secretory proteins (CRISPS), antigen 5 (Ag5) and pathogenesis-related 1 (Pr-1) (CAP) superfamily of proteins are found across the bacterial, fungal, plant and animal kingdoms. Although many CAP superfamily proteins remain poorly characterized, over the past decade evidence has accumulated, which provides insights into the functional roles of these proteins in various processes, including fertilization, immune defence and subversion, pathogen virulence, venom toxicology and cancer biology.Objective and Rationale: The aim of this article is to summarize the current state of knowledge on CAP superfamily proteins in mammalian fertility, organismal homeostasis and disease pathogenesis.Search Methods: The scientific literature search was undertaken via PubMed database on all articles published prior to November 2019. Search terms were based on following keywords: 'CAP superfamily', 'CRISP', 'Cysteine-rich secretory proteins', 'Antigen 5', 'Pathogenesis-related 1', 'male fertility', 'CAP and CTL domain containing', 'CRISPLD1', 'CRISPLD2', 'bacterial SCP', 'ion channel regulator', 'CatSper', 'PI15', 'PI16', 'CLEC', 'PRY proteins', 'ASP proteins', 'spermatogenesis', 'epididymal maturation', 'capacitation' and 'snake CRISP'. In addition to that, reference lists of primary and review article were reviewed for additional relevant publications.Outcomes: In this review, we discuss the breadth of knowledge on CAP superfamily proteins with regards to their protein structure, biological functions and emerging significance in reproduction, health and disease. We discuss the evolution of CAP superfamily proteins from their otherwise unembellished prokaryotic predecessors into the multi-domain and neofunctionalized members found in eukaryotic organisms today. At least in part because of the rapid evolution of these proteins, many inconsistencies in nomenclature exist within the literature. As such, and in part through the use of a maximum likelihood phylogenetic analysis of the vertebrate CRISP subfamily, we have attempted to clarify this confusion, thus allowing for a comparison of orthologous protein function between species. This framework also allows the prediction of functional relevance between species based on sequence and structural conservation.Wider Implications: This review generates a picture of critical roles for CAP proteins in ion channel regulation, sterol and lipid binding and protease inhibition, and as ligands involved in the induction of multiple cellular processes. [ABSTRACT FROM AUTHOR]

Background: Some venoms and their isolated compounds have been shown to have antibacterial properties. Snake, scorpion and bee venoms are a complex mixture of proteins such as phospholipase and melittin, which have an effect on bacterial growth inhibition. This study aimed to investigate of antibacterial effect of three different venoms against selected bacterial strains. Materials & Methods: Crude venoms obtained from snake (Echis carinatus), scorpion (Mesosobuthus epues) and bee (Apis mellifera) were selected. The crude venoms from these species was purified by using gel filtration chromatography and the molecular weights of the compounds in these venoms estimated by using SDS-PAGE. The approximate lethal dose values of venoms were determined. Antibacterial activity of venoms against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli were evaluated. Venoms and its isolated fractions and standard antibiotic were tested by using the disc diffusion method. Results: E. carinatus crude venom and fraction 2 were effective against S. aureus and E. coli. M. eupeus crude venom and fraction 1 and 4 were effective against B. subtilis. A. mellifera crude venom demonstrated antibacterial activity against E . coli, S. aureus and Fraction 3 of this venom has an inhibition effect for E. coli and S. aureus. Conclusion: Snake, scorpion and bee venoms inhibit the growth and survival of bacterial strains and that these venoms can be used as a complementary antimicrobial agent against pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Background and Purpose: Blocking the voltage-gated proton channel HV 1 is a promising strategy for the treatment of diseases like ischaemia stroke and cancer. However, few HV 1 channel antagonists have been reported. Here, we have identified a novel HV 1 channel antagonist from scorpion venom and have elucidated its action mechanism.Experimental Approach: HV 1 and NaV channels were heterologously expressed in mammalian cell lines and their currents recorded using whole-cell patch clamp. Site-directed mutagenesis was used to generate mutants. Toxins were recombinantly produced in Escherichia coli. AGAP/W38F-HV 1 interaction was modelled by molecular dynamics simulations.Key Results: The scorpion toxin AGAP (anti-tumour analgesic peptide) potently inhibited HV 1 currents. One AGAP mutant has reduced NaV channel activity but intact HV 1 activity (AGAP/W38F). AGAP/W38F inhibited HV 1 channel activation by trapping its S4 voltage sensor in a deactivated state and inhibited HV 1 currents with less pH dependence than Zn2+ . Mutation analysis showed that the binding pockets of AGAP/W38F and Zn2+ in HV 1 channel partly overlapped (common sites are His140 and His193). The E153A mutation at the intracellular Coulombic network (ICN) in HV 1 channel markedly reduced AGAP/W38F inhibition, as observed for Zn2+ . Experimental data and MD simulations suggested that AGAP/W38F inhibited HV 1 channel using a Zn2+ -like long-range conformational coupling mechanism.Conclusion and Implications: Our results suggest that the Zn2+ binding pocket in HV 1 channel might be a hotspot for modulators and valuable for designing HV 1 channel ligands. Moreover, AGAP/W38F is a useful molecular probe to study HV 1 channel and a lead compound for drug development. [ABSTRACT FROM AUTHOR]

Objective: Despite being a cardinal clinical sign of systemic sclerosis (SSc), digital pitting has been little studied. Our objective was to test, in a pilot study, the hypothesis that pitting is painful and associated with digital vascular disease severity.Method: Fifty patients with SSc were recruited: 25 with and 25 without digital pitting. Fingertip pain was assessed on a 0-10 scale. Thermography of both hands assessed surface temperature, allowing calculation of the distal-dorsal difference (temperature gradient) for each finger. Nailfold capillaroscopy was performed in each finger using a dermatoscope, and graded on a 0-3 scale (0 = normal; 3 = grossly abnormal).Results: In the 25 patients with digital pitting, 65 fingers in total were affected (mainly the index and middle fingers). Pain scores were higher in 'pitting' patients [median 4 (interquartile range 3-8) vs 0 (0-2), p < 0.001], and pitting patients reported that pitting impacted on activities of everyday living. Temperature gradients along the fingers did not differ significantly between patients with and without pitting (p = 0.248). Pitting patients were more likely to have 'grossly abnormal' capillaries than those without pitting, and less likely to have 'no/mild' nailfold capillary changes.Conclusions: Digital pitting is painful and impacts on hand function. Capillaroscopy findings provide further support for an association between pitting and severity of digital vascular change. Larger, more comprehensive studies are required to examine the pathophysiology of pitting and to pave the way to therapeutic intervention, ideally including preventive strategies. [ABSTRACT FROM AUTHOR]

Scorpion envenomation is common in the tropical and subtropical regions. It poses a major public health problem with some patients having serious clinical manifestations and severe complications including death. Old World and New World scorpions are usually contrasted because of differences in venom composition, clinical presentation and severity, and, accordingly, different therapeutic approaches. The majority of scorpion stings are either dry or result in low amounts of injected venom, thus explaining why up to 95% of scorpion stings ensue only in local signs. For a clinical envenomation to occur, it has been suggested that the interaction between the quantity of venom introduced in the body of the prey and the distribution volume should ensue in a critical threshold of scorpion toxin plasma concentration. In this case, there is a massive release of neurohormonal mediators (mainly catecholamine), with systemic vasoconstrictor effects eliciting a sharp increase in systemic arterial pressure and LV-filling pressure and decreased cardiac output. This early phase of cardiac dysfunction, also called "vascular phase", is followed by a severe cardiomyopathy, a form of Takotsubo cardiomyopathy, involving both ventricles and reversible in days to weeks. The more comprehensive understanding of the disease pathophysiology has allowed for a well-codified symptomatic treatment, thus contributing to a substantial reduction in the death toll of scorpion envenomation over the past few decades. The standard intensive-care treatment (when available) overcomes envenomation's consequences such as acute pulmonary edema and cardiogenic shock. Even though it continues to inspire many evaluative studies, immunotherapy seems less attractive because of the major role held by mediators in the pathogenesis of envenomation, and unfavorable pharmacokinetic properties to existing sera compared to venom. Meta-analyses of controlled trials of immunotherapy in severe scorpion envenomation reached similar conclusions: there is an acceptable level of evidence in favor of the use of scorpion antivenom (Fab'2) against Centruroides sp. in USA/Mexico, while there is still a need for a higher level of evidence for immunotherapy in the Old World envenomation. [ABSTRACT FROM AUTHOR]